Operational Biosurveillance

The Use of Forecasting to Rapidly Identify Non-Routine Infectious Disease Signatures: Part 2

Our team has been doing a full review of outpatient / inpatient / transfer stats from our department's perspective for Jan-Mar 2012, which was a time period where we saw an epidemic of human metapneumovirus (hMPV) that overlapped an unusually severe season of RSV. We have issued several reports of our experience here in this blog.  In Part 2, we explore further the "so what" of operational infectious disease forecasting coupled to early warning. 

On the 25th of every month the Ascel Bio Black Canyon Infectious Disease Forecasting Station released forecasts for infectious disease activity specific to our county.  RSV and other respiratory pathogens were therefore expected to appear and cause a given level of strain to our medical infrastructure. 

From Jan 4th to Feb 10th, we admitted a low number of patients exhibiting typical RSV infection, where we followed American Academy of Pediatrics (AAP) guidelines for the management of RSV: no antibiotics, steriods, with the rare use of inhalers.  In the midst of these admissions, the Station issued an advisory for unusual human metapneumovirus activity which at the time was primarily disruptive to the outpatient component of our medical infrastructure.

Then, from Feb 12-16th, multiple back to back admissions presented as typical RSV infections but abruptly decompensated on the floor, precipitating transfers for all of them to the Front Range by fixed wing aircraft.  In the midst of this, we were told the Front Range's PICU grid capacity was close to diversion status.  It was during this time we had report from the PICU that received our patients they were coinfected with Haemophilus influenzae.  One of these patients would later be triply infected with Streptococcus pneumoniae while intubated.

On Feb 18th, a warning was issued by the Station, indicating an unusual epidemiological situation now existed for epidemic RSV of high clinical severity.  Our department issued guidance to abandon standard AAP protocol for the treatment of RSV and consider the use of antibiotics prophylactically given the apparent high coinfection rate being seen.

Results:

Before the warning was issued to all providers with pediatric admitting privledges, our hospital exhibited a 33% transfer rate, all of whom were over the course of four days.  Of those transferred, none of the patients were given antibiotics prophylactically upon admission.  Forty-six percent of all admissions pre-warning were provided antibiotics for comorbid conditions such as otitis media.

After the warning was issued, the transfer rate dropped to 8%, as now 88% of RSV admissions were provided antibiotics prophylactically.  Of total admissions to the hospital during the entire epidemic of RSV, 71% of the admissions were seen during the post-warning period.  The 8% who were transferred were placed on antibiotics prophylatically, however it is not clear they were truly infected with RSV.

Adherence to the Station's warning heeded at least a 76% reduction in transfer rates due to RSV during the epidemic. 

This is one of the rare examples of operational validity and proof of performance using near real time surveillance coupled to operational forecasting that altered the outcome of an epidemic.

 

 

 

 

 

 

 

Detection And Warning Of Biotech Accidents

The recent, ongoing controversy about genetic experimentation with pathogens of high potential consequence for global health raises serious questions about our global capability and capacity to 1) detect events associated with accidents of biological technology ("biotechnology"); 2) recognize those signatures; and 3) issue timely warning of such phenomenon to the world in a transparent process free of political tendencies to withold information. 

First, please refer to prior posts on the difference between signature detection, recognition, and warning.  Here we define capability as the inherent knowledge of how to execute the analytic discipline of biological signature detection, recognition, and warning; and capacity as the global load factor for capability, where obviously a single analyst cannot possibly watch the entire planet.

In regards to the recent reports of deliberate genetic experimentation with H5N1 virus, the root question that should have been asked by the media and anyone astutely watching the controversy is why did the US National Institutes of Health (NIH) authorize the expenditure of US taxpayer funds for the experiment in the first place? 

Funding from NIH does not happen magically.  One has to respond to a Request For Proposals (RFP) with a formal proposal that includes a detailed description of the experiment that is to take place and the justification for that experiment.  There is a rather uncomfortable question to be asked of Dr. Fauci and his staff that goes something like this: "Were you aware of the nature of the experiments about to be conducted by these researchers using US taxpayer funds before the experiments were actually executed?"

However unlikely, it is a well-documented fact that the more infectious an agent, the more likely it is to infect laboratory workers.  In this particular case, the probability for an infection to occur was likely neglible, but there nonetheless.  And trust that the world's public will not accept any excuse should the unthinkable have happened: a laboratory accident that triggered a community outbreak.  The terrible juxtaposition of the highly improbable with the unthinkable consequence again raises its head.

So let's play this scenario out: what is the global capability and capacity to pick up on these kinds of events?  This question is asked because, if we are to believe then the NIH failed to recognize the risk in conducting these experiments in the first place, then how fast do we honestly think we as a global community would have recognized the "oops" should the virus have infected one of the laboratory workers... a worker that went home that night to expose others?  How many chains of transmission would have occurred before it would have been picked up by an astute physician or public health analyst?  How fast would the dots have been connected to trace back to this being an engineered H5N1?  How fast would seed stock have been secured for vaccine production companies?  How fast would those companies be able to grow vaccine stock and execute distribution? 

The answers are very, very bad and uncomfortable.  Let's give some additional data points:

1.  The discovery of Marburg virus in Germany, 1967.  This was a laboratory accident involving a previously unknown lethal, transmissible virus.  Exposed laboratory personnel went home to their families and in turn exposed them.  Note the initial diagnostic confusion, calling the disease "yellow fever", then "monkey disease":

                     Aug 23, 1967                                                                        Sept 13, 1967

 

2.  Laboratory Accident Historical Surveys

It is useful to review the historical records of laboratory accidents.  Figure 1 displays the top diseases and pathogens that infected and killed laboratory workers in the United States from 1930 to 1950, the results of the most comprehensive survey of its kind, conducted by Sulkin and Pike in 1951.

[a]

[b]

Figure 1.  Laboratory infections [a] and case fatality rates [b] by agent / disease for civilian laboratories in the United States from 1930 to 1950.  This is a sampling of the original data.  The entry titled “encephalitis” refers to infections by Western (1), Eastern (1), and Venezuelan (11) equine encephalitis viruses and Russian Far East encephalitis virus (1).  Infections were due to other pathogens as well.

Figure 1 represents a sampling of the total list of agents involved in reported laboratory infections.  Other agents and diseases included:

• actinomycosis
• ascariasis
• B virus
• blastomycosis
• dengue
• giardiasis
• glanders
• gonorrhea
• hookworm
• influenza
• leishmaniasis
• leptospirosis
• louping ill
• measles
• meningococcal meningitis
• mumps
• non-typhoidal salmonella
• Pasturella species
• pinworm
• plague
• ringworm (Candida)
• Rocky Mountain spotted fever
• schistosomiasis
• Serratia marcescens
• sporotrichosis
• Streptococcus pneumoniae
• strongyloidiasis
• syphilis
• tetanus
• vaccinia
• vesicular stomatitis
• viral diarrhea

All manner of infectious agents and their byproducts such as toxins have essentially posed risk for laboratory workers not protected by Biological Safety Cabinets, negative pressure rooms, proper handling protocols, or vaccine.  During the time period covered by the survey, there were few vaccines or antibiotics to mitigate exposure.  It is believed the survey was a gross underestimate of the true number of infections.  There was no systematic reporting mechanism to report laboratory infections in the United States at the time, as is the case now. 

Singh provided an updated perspective based on Pike’s survey in 1976, as shown in Figure 2. 

[a]

[b]

Figure 2.  Laboratory infections [a] and case fatality rates [b] by agent / disease for civilian laboratories in the United States based on updated assessments by Pike in 1976.  This is a sampling of the original data.

When considering biological weapons programs, new hazards were introduced relating to handling of aerosols, mass production, and deployment testing of live agents.  Figure 3 provides summaries of laboratory infections in Fort Detrick personnel during the years of the active United States biological weapons program (1943-69).

[a]

[b]

[c]

[d]

[e]

Figure 3.  Laboratory infections during the years of the active American biological weapons program (1943-1969), showing annual infections due to anthrax [a], tularemia [b], brucellosis [c], Q fever [d], and Venezuelan equine encephalitis [e]. In the case of Venezuelan equine encephalitis, an ineffective live attenuated vaccine candidate was responsible for a number of infections.  Use of Biological Safety Cabinets began in 1950.  Anthrax vaccine was available beginning in 1952.  Tularemia vaccine was available beginning in 1958.  Brucellosis research was decreased beginning in 1953; no vaccine was available.  A vaccine for Q fever was available in 1965.  The TC-83 live attenuated Venezuelan equine encephalitis vaccine was available in 1963.

Other agents and diseases were responsible for laboratory infections at Fort Detrick such as:

• plague (pneumonic)
• glanders
• psittacosis
• botulinum toxin
• staphylococcal enterotoxin B

Aside from the obvious increased risk for a laboratory accident being related to handling live agents, there are several risk characteristics worth noting:

• the infectious agent:
  • causes clinically significant disease in humans
  • is considered a disease of public health significance (especially from an international perspective)
  • is associated with a low infectious dose
  • transmits efficiently from person to person
  • there is no or minimal availability of vaccine, antibiotic, or other effective medical countermeasure
• the laboratory environment:
  • produces or works with aerosols
  • does not utilize Biological Safety Cabinets, negative pressure rooms, hazard suits for personnel, or other protective mechanisms
  • has laboratory workers unfamiliar with proper handling protocols for the agent in question

3.  The epizootic of Venezuelan Equine Encephalitis in Venezuela and Colombia, 1995.  This was a significantly disruptive epidemic involving an estimated 100,000 people that peaked at the same time as a seasonal peak in direct, non-stop air traffic to Florida in 1995.  This was yet another example of warning failure due to failure to detect, recognize, and warn.  Most poignant was the hypothesis the epizootic was due to a laboratory accident- a hypothesis posed only years after the fact.

Download Blake et al VEE in 1995

4.  The accidental distribution of influenza A/H2N2 sample panels:

CAP, the American Association of Bioanalysts, the American College of Family Physicians and the American College of Physician Services all sent proficiency testing surveys containing one or more samples of A/H2N2 to approximately 6,500 labs in the United States. Proficiency testing panels containing A/H2N2 samples were also sent to laboratories in Belgium, Bermuda, Brazil, Canada, Chile, France, Germany, Hong Kong, Israel, Italy, Japan, Lebanon, Mexico, Saudi Arabia, Singapore, South Korea and Taiwan. The World Health Organization has informed the Ministries of Health in these countries.

5.  The still-open case of possible ongoing transmission of polio vaccine-derived virus type 1 in Haiti.  Here translocation of a suspect case to North Carolina went completely undetected by North Carolina's public health officials, CDC, and PAHO/WHO.  The context of social outcry over the suspected accidental introduction of cholera by the United Nations to Haiti provided a strong disincentive for officials to carry out a complete investigation.  The still-open question is whether deployment of Sabin / oral live attenuated polio vaccine in Haiti resulted in the escape of what may be, in essence, an accident of biotechnology out in Haiti's ecosystem continuing to recombine with native enteroviruses.  The lack of a credible investigation into this question remains a concerning point of accountability for PAHO and CDC.  Even more concerning is the multi-million dollar industry interest in continuing to produce, distribute, and vaccine people in extremely vulnerable areas of the world with this agent that has a well-documented nasty habit of causing transmissible disease.

These of course are but some of many examples and observations related to the concern of the proliferation of biological technology.  Accidents should be expected as human-driven processes and procedures are fallable by nature.  And politics certainly have, do, and will cloud situational awareness.

 

 

Biosurveillance: The Difference Between Detection, Signal Recognition, and Warning

For the last 15 or so years, we have seen an explosion of different electronic disease surveillance systems emerge.  Everything from laboratory diagnostics and reporting systems to syndromic surveillance to using the internet for so-called "event-based surveillance".  And there has been a virtual orgy of academic frenzy around the "bright lights and shiny object" effect of the technology.  This is representative of billions of taxpayer dollars over these years dispensed from a variety of federal mechanisms.

Yet, with all of this expenditure (much of which is ongoing), we have still so very little proof of operational value.  The "research and development ice cream cone" continues to lick itself without any apparent metric held by the funders for the operational "so what".  Arthur Reingold's challenge points from 2003 still appear to be unanswered ten years later.  Below, his points have been adjusted to fit a more broad consideration of the topic:

1. Demonstrating that [x, y, z type of] surveillance reduces morbidity and / or mortality following [an infectious disease crisis / disaster].
2. Types of [infectious disease crises / disasters] that [x, y, z type of] surveillance is likely to detect.
3. Response to apparent increases in illnesses signaled by [x, y, z type of] surveillance.
4. Plausibility that [x, y, z type of] surveillance can yield more timely identification of the population at risk in [an infectious disease crisis / disaster].
5. Likelihood that [x, y, z type of] surveillance will produce useful information about naturally occurring infectious diseases.
6. Circumstances under which [x, y, z type of] surveillance is likely to strengthen local and state health departments.

Certainly Reingold was not the only person during the heyday of syndromic surveillance to raise questions about the validity of the approach, but the gist of the above challenges were echoed several times in the literature.  But the academics lept onward undeterred, and the marketing associated with their programs grew to astounding levels of claimed accomplishments.

One such claim was that made by John Brownstein of HealthMap on Aug 3rd at an IARPA OSI Program Proposer's Day, who stated (paraphrased) that HealthMap was "the first surveillance system in the world to detect and publicly report the 2009 H1N1 influenza pandemic".  This impressive claim invokes scrutiny into the defintion of detection and how it applies to evaluating any disease surveillance system... and of course, the taxpayer funds associated with that program.

Merriam Webster defines the word detect as

1. to discover the true character of;
2. to discover or determine the existence, presence, or fact of
   

Webster's definition of recognize goes deeper than detect, however:

1. to acknowledge formally;
2. to acknowledge or take notice of in some definite way;
3. to perceive to be something or someone previously known

However it is the word's Latin origin, cognoscere that brings this point into focus.  Cognoscere means to know.  Of course the word know implies that a human being's mental processes have been engaged.  Which implies 1) there is a human being looking at the data and thinking about it. 

The definition of warning is provided by Webster as:

1. to give notice to beforehand especially of danger or evil
2. to give adminishing advice to
3. to call to one's attention

So this implies a human being, having thought about the data, has recognized and prioritized a concern... and communicated that specific concern to others.

The analytic team that warned the senior health intelligence officer in CDC's Director's Emergency Operations Center (DEOC) noted at the time that HealthMap's information was 1) not posted on their website as fast as the original Mexican source posting 2) was not highlighted in any unusual way to call singular attention to the information among dozens (hundreds?) of other colored pins on their map, and 3) where was no transfer of information to ProMED or CDC from HealthMap evident to suggest that human beings had communicated about the information during early to mid April 2009.  Therefore, the following may be concluded:

1. The first point of detection was actually the Mexican journalist who wrote the first article on the La Gloria situation.  HealthMap simply functioned as a Google News parser- a function anyone could have performed using Google Alerts.  If you happened to click that one pin on the map, you would have 'seen' the report, albeit then you would have to understand whether what was being reported was unusual...
   
2. Human beings were required to recognize unusual indicator patterns in the initial reports (n=1 to 3), not through recognition of simply volume of reporting as captured by HealthMap's Heat Index. 
3. Human to human communication clearly had to occur to push the warning through, as information provided via pull websites and push email notifications were inadequate due to daily information overload at WHO and CDC.

The point of the above is not to singularly criticize HealthMap but to make a point: collection of data is insufficient, by itself, to generate operational impact.  This was a very hard lesson learned by the syndromic surveillance community as well.  And if you are fighting an embedded, decades-old professional culture imbued with a "not invented here" bias (i.e. public health), it is unlikely the data will be exploited properly.

So let's give Brownstein a break for a minute and focus on one of his collaborators: the Canadian Global Public Health Network (GPHIN).  Brownstein's claim at the IARPA meeting was a duplication of GPHIN's claim to the world of having been the first public health system to detect SARS (see attached manuscript, Figure 1). However there was unverified rumor at the time that the web-harvested Chinese media article published on Nov 27, 2002 went unnoticed by GPHIN's staff for some time due to lack of machine translation for Chinese (unverified) and lack of a Chinese linguist.  Even if these rumors were false, and GPHIN's system immediately punched a warning out to its customers, there is no evidence anyone was paying attention.  In the multiple manuscripts and powerpoints given by GPHIN staff, not one contains copies of emails or phone records to indicate human beings had 1) recognized the problem, 2) prioritized the problem (out of the dozens of other reports for the day), and 3) communicated directly with the Canadian PHAC, the US CDC, or WHO specifically about this prioritized problem.  This is concerning when considering how much information was actually missed at the time (see attached report by Polyak et al).

The analogy is football: it's like being thrilled you threw a "Hail Mary" pass, but unawares that 1) no one caught the ball and 2) ran it to the end zone... 3) and thus you lost the game in the process.  Sound familiar?  It should.  These are very similar issues to those in the original 9/11 Commission Report.

Currently the federal government continues to chase its tail, spending more funds on biosurveillance research: the self-licking ice cream cone.  Billions of dollars and 10-15 years later, we still are not holding these systems' collective feet to the fire asking "show me don't tell me".  We continue to reach for the bright lights and shiney objects represented by the latest fad technology ("social media" being the current one) without thinking about how to promote the human process of understanding the data, accumulating knowledge, and using that knowledge to impact the potential outcome of the threat.

These are lessons currently highlighted in the recent IOM report on the DHS National Biosurveillance Integration Center (NBIC), however the problem is far bigger than just NBIC, DHS, or the people funded by DHS.  This is a biosurveillance community-wide problem that affects the credibility of the entire field. 

And if we do not fix it, the funding and public support may eventually disappear.

Download GPHIN Manuscript

Download Emergence of SARS in 2002

 

 

 

More Evidence of Human-Human Transmission of Swine-Origin Triple Reassortant Influenza A(H3N2) Virus In The United States

On December 23rd, CDC released another statement about the evolving situation with swine-origin triple reassortant influenza A(H3N2) virus in the United States.  Three more human infections, two of which associated with a daycare in West Virginia.  The latter is of greater concern than the former due to probable human-human transmission.  Time delays between submission of samples and public report by CDC remain high:

(Case A) Indiana, no evidence of human-human transmission- exposure from swine. 

• Day 0 (Oct 20th).  Patient symptomatic, hospitalized for 4 days.
• Day 2 (Oct 22nd).  Influenza-positive per in-house hospital laboratory testing.
• Day 8 (Oct 28th).  Indiana State Public Health Laboratory: "inconclusive influenza A virus".
• Day 11 (Oct 31st).  CDC confirms via genomic sequencing presence of "A(H3N2)v" (formerly known as S-OtrH3N2)
• Day 64 (Dec 23rd).  CDC publicly releases the above information.
• Summary:
  • Time delta: state public health recognition of unusual virus= 8 days
  • Time delta: clinical processing of patient to CDC awareness= 11 days
  • Time delta: CDC issuance of warning to the public= 64 and 56 days from initial clinical processing of the patient and state notification to CDC, respectively

(Cases B) West Virgina, evidence of human-human transmission.

• Day 0 (Nov 12th, approximate).  Pediatric patient recognized symptomatic by parents.
• Day 7 (Nov 19th).  Patient, who was already hospitalized for an unrelated issue, develops fever.
• Day 9 (Nov 21st).  Sample taken.  In-house hospital laboratory discovers sample is positive for influenza A.  Patient discharged home.
• ... No further information regarding when West Virginia's state laboratory or CDC processed the sample, which was A(H3N2)v-positive.
• Summary:
  • Time delta: state public health recognition of unusual virus= unknown
  • Time delta: clinical processing of patient to CDC awareness= unknown
  • Time delta: CDC issuance of warning to the public= 34 days from initial clinical processing of the patient (approx. Nov 19th) 

(Case C) West Virginia, same cluster / thread.

• Day 0 (Nov 29th).  2nd child at daycare center ill.
• Day 9 (Dec 7th).  West Virginia Office of Laboratory Services processes sample as "inconclusive"- forwards on to CDC.  This patient was part of a retrospective assessment, where clinical processing did not occur.
• .. No further information regarding when CDC processed the sample, which was A(H3N2)v-positive.
• Summary:
  • Time delta: CDC issuance of warning to the public= 34 days from state public health laboratory processing of the sample to CDC issuance of public warning

 

The key point is of course, we only know what we are able to know.  Our team leaned into the discussion in November to ensure CDC was aware we were 1) monitoring the situation and 2) are carefully documenting their performance in coupling warning to response.  And quietly behind the scenes we are engaging clinical practitioners in an effort to encourage more sampling among symptomatic patients who were vaccinated for this season.  We expect the predominance of this focus to be on pediatric patients, however we are not seeing social sensitization yet among pediatricians.  Messaging from CDC requires clarification and guidance regarding when to sample.

Currently, we are observing between large time deltas between clinical processing of these patients and CDC's issuance of public warning.  It is our opinion that if A(H3N2)v suddenly displaces current seasonal A/H3N2 or gains significant prevalence, the first point of recognition may be an abruptly overwhelmed pediatric medical infrastructure versus dramatically time-delayed reporting from CDC. 

The observations of public health performance during the 2009 influenza pandemic begin to repeat themselves...

 

Analysis of Warning Process: Swine-Origin Triple Reassortant Influenza A(H3N2) Virus In USA

We have been monitoring the situation with swine-origin triple reassortant influenza A(H3N2) virus (S-OtrH3N2) inside the United State for some time now.  Recent reports of likely human-human transmission sparked debate, discussed here in this post.

1.  First, the ECDC's risk assessment was an excellent discussion of the situation.  CDC's report may be found here.

2.  The time delays in issuing statements about the evolving situation reflect the forensic process and length of time it takes to recognize novel pathogens and execute public warning inside the United States.  In this case, a joint press releaseon Sept 2nd and 5th, respectively, from CDC and Pennsylvannia state officials announced recognition of S-OtrH3N2 pediatric cases in Indiana and Pennsylvania stemming from exposure to infected swine.  The breakdown of timelines as follows:

Case A (Indiana):

• Day 0 (July 23rd).  Parental recognition of a child with flu-like illness.  Child brought to local ED, clinical laboratory testing at the hospital positive for type A influenza.   Child found to have been vaccinated the prior fall, had chronic medical condition, discharged from the ED same day without anti-virals.
• Day 1 (July 24th).  Child returns to ED with a worsened clinical picture and admitted.
• Day 4 (July 27th).  Child does well and is discharged from the inpatient ward to home.  No further issues.
• Day 25 (Aug 17th).  Indiana State Department of Health Laboratories test the sample and discover suspect swine-origin influenza A (H3N2) virus.  CDC notified and sample forwarded to CDC for confirmation and further analysis.
• Day 27 (Aug 19th).  CDC confirms findings of the Indiana State DOH Lab. 
• Day 41 (Sep 2nd).  CDC reports publicly results of genomic sequencing: swine-origin triple reassortant influenza A(H3N2) virus that now includes segments of 2009 pandemic H1N1 virus.  Report indicates patient had contact with infected swine.
• Summary:
  
  • Time delta: state public health recognition of unusual influenza virus= 25 days
  • Time delta: clinical processing of patient to CDC awareness= 25 days
  • Time delta: CDC issuance of warning to the public= 41 and 14 days from initial clinical processing of the patient and state notification to CDC, respectively
    

Case B (Pennsylvania):

• Day 0 (Aug 20th).  Parental recognition of symptoms, take child to local ED.  Nasal swab positive for influenza A.  Child was vaccinated the prior fall.
• Day 3 (Aug 23rd).  Pennsylvania State Department of Health Laboratory idenifies suspected swine-origin influenza A (H3N2) virus.
• Day 4 (Aug 24th).  Pennsylvania state officials notify CDC of the findings.
• Day 6 (Aug 26th).  CDC confirms findings.
• Day 13 (Sep 2nd).  CDC reports publicly results of genomic sequencing: swine-origin triple reassortant influenza A(H3N2) virus that now includes segments of 2009 pandemic H1N1 virus.  Report indicates patient had contact with infected swine.
• Summary:
  • Time delta: state public health recognition of unusual influenza virus= 3 days
  • Time delta: clinical processing of patient to CDC awareness= 4 days
  • Time delta: CDC issuance of warning to the public= 13 and 7 days from initial clinical processing of the patient and state notification to CDC, respectively

Questions were asked openly of CDC, USDA, and Pennsylvania state officials on Sept 12th about how these cases were recognized.  More to the point, guidance for clinical sampling was requested publicly.  This request was never answered.  At this point, the situation had migrated to the top of biological threat monitoring list.  Lack of response was not reassuring.

On Nov 23rd, a probable human-human transmission cluster of S-OtrH3N2 cases was reported by CDC, with an evident 7-10 day lag between initial clinical processing, laboratory based recognition at the state level, and CDC issuance of a public statement.  This was a much better time delta and likely reflective of surveillance grid sensitization this particular issue. 

Overall, we see a drop from a time delta between clinical processing and CDC issuance of public warning of these events from 41 to 13 to 7 days as the situation evolved.  It was not until Nov 26th did media reports indicate a seed strain had been sent to vaccine manufacturers in case S-OtrH3N2 begins to overtake current circulating strains of influenza virus in the human population.

There are several summary observations to make at this point:

1. S-OtrH3N2 is our #1 pathogen of concern for the United States and the world at this time, from the perspective of potential social disruption.  Projected impact would be similar to that seen in a vaccine drift year of seasonal influenza (e.g. 2004 in the United States).  Thus far no fatalities have been observed, but the sample size is far too small at this time to make firm assertions of case fatality rate or morbidity profiles. 
2. CDC should be praised for proactively forwarding seed stock to vaccine manufacturers.  What will be interesting to observe at this point is the time delta between initial recognition of sustained human-human transmission and an order to ramp up and distribute S-OtrH3N2 vaccine to local healthcare providers.  In this instance CDC stands in much better position to execute more efficient warning to response operational coupling.
3. The above said, we note with great concern how long it took to recognize and effectively communicate to the public the initial situation in Indiana.  From the perspective of this author, a pediatrician practicing in a rural setting, there is no healthcare provider sensitization to this issue- i.e. there is no change at all in sampling procedures for children presenting with influenza-like illness.  It is as though this season is like any other.  Especially after the 2009 H1N1 pandemic experience and the current economic recession, we observe a general reluctance to test for influenza unless there is a compelling reason to do so.
4. Not all states have the surveillance capabilities of Pennsylvania and Iowa.  There is an incomplete understanding of how pervasive S-OtrH3N2 transmission is inside the United States at this time. 
5. Abrupt community inundation of pediatric flu-like illness, especially among children previously vaccinated for the 2010-2011 influenza season, should prompt an index of suspicion at least to obtain samples for testing by clinicians.  Submission of samples that are processed by state laboratories and moved up the chain to CDC is the only way to assess this evolving situation accurately.